Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates, and the tissues of some invertebrates. The chemical formulae of hemoglobin vary widely across species, and even slightly among subgroups of humans. In adult humans, the most common hemoglobin type is a tetramer called hemoglobin A. Hemoglobin A consist of non-covalently bound α and β subunits. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Hemoglobin variants are a part of the normal embryonic and fetal development, but mutant forms of hemoglobin in a population, may also be caused by variations in genetics. Some well-known genetic hemoglobin variants are responsible for diseases such as sickle-cell anemia. A separate class of diseases known as thalassemias are caused by underproduction of normal and abnormal hemoglobin and also, through problems with and mutations in globin gene regulation.
To a small extent, hemoglobin A slowly combines with glucose at the terminal valine of each β chain and the resulting molecule is often referred to as HbAlc. As the concentration of glucose in the blood increases, the percentage of hemoglobin A that turns into HbAlc increases. In diabetics whose glucose usually runs high, the percent HbAlc also runs high. Long-term control of blood sugar concentration can be measured by the concentration of HbAlc. A higher glucose concentration results in more HbAlc. Because the reaction is slow, the HbAlc proportion represents glucose level in blood averaged over the half-life of red blood cells, is typically 50-55 days.
Diabetes mellitus commonly known as diabetes, is a group of metabolic diseases resulting in abnormally high blood sugar levels referred to as hyperglycemia. Blood glucose levels are controlled by a complex interaction of multiple chemicals and hormones in the body, including the hormone insulin. More specifically, Diabetes mellitus refers to a group of diseases that lead to high blood glucose levels due to defects in one of insulin secretion or insulin action. Type 1 diabetes is a consequence of a diminished production of insulin while Type II and gestational diabetes are resistant to the effects of insulin. Type II diabetes is the most prevalent form of diabetes. Type II diabetes is often asymptomatic in its early stages and can remain undiagnosed for many years. Diabetes and its treatments can cause many complications. Acute complications exemplified by hypoglycemia, ketoacidosis, or nonketoticii hyperosmolar coma, may occur if the disease is not adequately controlled. Serious long-term complications due to diabetes may include cardiovascular disease, chronic renal failure, retinal damage which can lead to blindness, several kinds of nerve damage, and micro-vascular damage, which may cause erectile dysfunction and poor wound healing. In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults.
There is often a long, latent, asymptomatic period during which people with Type II diabetes are undiagnosed. Most people are unaware they have Type II diabetes, but experience physiological complications from the disease. Many newly diagnosed Type II diabetes cases already show evidence of micro-vascular complications and serious effects and long term complications from the disease. Early detection of diabetes is essential and may help improve the outcome for people with Type II diabetes. Regular screening for diabetes will enhance quality and length of life for a diabetic person from reducing the severity and frequency of immediate effects or prevention and/or delay of long term complications.
Glycated substances are eliminated from the body slowly. Red blood cells, which have a consistent lifespan of 120 days, are easily accessible for measurement of recent increased presence of glycating product. This fact is used in monitoring blood sugar control in diabetes by monitoring the glycated hemoglobin level, also known as HbAlc. Measurements of HbAlc in the 4-6% range are considered normal, less than 7% is a well controlled diabetic, 7-8% is an average diabetic and greater than 8% is a poorly controlled diabetic. There are many known methods to screen for diabetes. The fast plasma glucose and oral glucose-tolerance tests are standard clinical tests. The fast plasma glucose test is measured in a blood sample taken after eight hours of complete fasting. The blood glucose tolerance test is measured in several blood samples taken at a series of intervals following the administration of a specific glucose load. A current screening method referred to as the plasma glucose test does not require fasting and includes a blood and/or urine test that measures plasma glucose levels with enzymatic assay. Another common screening method is to screen the blood for glycated hemoglobin (HbAlc) which is either based on charge difference between non-glycated and glycated hemoglobin using ion-exchange chromatography, electrophoresis, or isoelectric focusing or immunological methods employing antibodies against glycated N-terminal of β-chain of the hemoglobin. Recently, the first molecular assay for glycated hemoglobin was disclosed. The β-chain of hemoglobin was digested with Glu-C, providing an N-terminal hexapeptide which was measured using ElectroSpray Ionization Liquid Chromatography Mass Spectrometry (ESI-LC/MS). The current methods to screen and monitor for diabetes are expensive, laborious, and time-consuming, require highly skilled operators, unreliable, and often require repeat testing.
There are many types of known hemoglobin (Hb) molecules and many are associated with inherited blood disorders such as sickle cell, hemoglobin C, S—C, and E, thalassemia and analbuminaemia. The most common hemoglobin molecules are HbA, HbA2, HbF, HbS, HbC, Hgb H, and Hgb M. Healthy adults only have significant levels of HbA and HbA2. Some people may also have small amounts of HbF, which is the main type of hemoglobin in an unborn baby's body and certain diseases are associated with high HbF levels. HbS is an abnormal form of hemoglobin associated with sickle cell anemia. In adults, these hemoglobin molecules make up the following percentages of total hemoglobin. Hgb A1: 95% to 98%, Hgb A2: 2% to 3%, Hgb F: 0.8% to 2%, Hgb S: 0%, Hgb C: 0%. In infants and children, these hemoglobin molecules make up the following percentages of total hemoglobin, Hgb F (newborn): 50% to 80%, Hgb F (6 months): 8%, Hgb F (over 6 months): 1% to 2%. The presence of significant levels of abnormal hemoglobins may indicate hemoglobin C disease, rare hemoglobinopathy, sickle cell anemia, and thalassemia.
In general, people with these inherited blood disorders are physiologically vulnerable and are at higher risk of infection, stroke, heart failure, liver and acute chest syndrome. The current method to screen and monitor for blood disorders is the hemoglobin electrophoresis diagnostic test. This test is a widely used screening test and if the presence of the blood disorder is indicated, a second hemoglobin electrophoresis diagnostic test is preformed to confirm the first diagnosis. The current test that is used to screen and monitor for blood disorders is expensive, laborious, and time-consuming, require highly skilled operators, unreliable, and requires repeat testing.